: Liver diseases are a global health concern. Many in vitro liver models utilize cryopreserved primary human hepatocytes (PHHs), which commonly undergo post-thaw processing through colloidal silica gradients to remove debris and enrich for a viable PHH population. Post-thaw processing effects on healthy PHHs are partially understood, but the consequences of applying disease-origin PHHs to post-thaw density gradient separation have not been described.
View Article and Find Full Text PDFPerturbation of thyroid hormone (T) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based approaches that recapitulate thyroid cellular architecture and T production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p'1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T expression and inhibition by prototype thyroid disrupting chemicals (TDC).
View Article and Find Full Text PDFObjective: Lower socioeconomic status (SES) can accelerate immune aging; however, it is unknown whether and how lifespan socioeconomic context (SEC)-the relative wealth and quality of the communities an individual lives in across their lifespan-impacts immune aging. We examined the effects of childhood and adulthood SEC on late-differentiated immune cells and investigated the mediating and moderating role of cytomegalovirus (CMV), a key driver of immune aging.
Methods: Adults 60 years and older ( N = 109) reported their addresses from birth to age 60 years, which were coded for county-level employment, education, and income to construct a latent SEC variable, averaged across ages 0 to 18 years (childhood SEC) and 19 to 60 years (adulthood SEC).
Finding a long-term, human-relevant culture model for primary human hepatocytes (PHHs) for pharmacological and toxicological studies remains a challenge. Current in vitro model platforms are often inconvenient and complex, lack phenotypic stability over time, and do not support multiple PHH lots, lacking experimental reproducibility and flexibility. Here, we provide a detailed protocol for the thawing, plating, and maintenance of an all-human 2D+ hepatic system (TV2D+), which takes advantage of standard two-dimensional (2D) culture techniques and equipment while maintaining the longevity and phenotypic stability over time that typically accompany more complex three-dimensional (3D) systems.
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